title: Transglutaminase 6 interacts with polyQ proteins and promotes the formation of polyQ aggregates.
abstract: A common feature of polyglutamine (polyQ) diseases is the presence of aggregates in neuronal cells caused by expanded polyglutamine tracts. PolyQ proteins are the substrates of transglutaminase 2, and the increased activity of transglutaminase in polyQ diseases suggests that transglutaminase may be directly involved in the formation of the aggregates. We previously identified the transglutaminase 6 gene to be causative of spinocerebellar ataxia type 35 (SCA35), and we found that SCA35-associated mutants exhibited reduced transglutaminase activity. Here we report that transglutaminase 6 interacts and co-localizes with both normal and expanded polyQ proteins in HEK293 cells. Moreover, the overexpression of transglutaminase 6 promotes the formation of polyQ aggregates and the conversion of soluble polyQ into insoluble polyQ aggregates. However, SCA35-associated mutants do not affect their interactions with polyQ proteins. These data suggest that transglutaminase 6 could be involved in polyQ diseases and there may exist a common pathological link between polyQ associated SCA and SCA35.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Guan
authors.forename: Kai-De
authors.initials: KD
authors.lastname: Xia
authors.forename: Yan-Tao
authors.initials: YT
authors.lastname: Ma
authors.forename: Yu-Tao
authors.initials: YT
authors.lastname: Liu
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Shi
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Jia-Da
authors.initials: JD
authors.lastname: Li
authors.forename: Bei-Sha
authors.initials: BS
authors.lastname: Tang
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Wang
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D012995:Solubility; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D010455:Peptides; C097188:polyglutamine; C532876:TGM6 protein, human; D011503:Transglutaminases
keywords: Aggregates; PolyQ; SCA; Transglutaminase 6